The Acute Bronchodilator Effects of a Single Dose (2 Puffs) of the Shortacting Anticholinergic Ipratropium Bromide (40μg) and the Short-acting Beta-adrenergic Fenoterol (200μg) in Comparison to Placebo on Top of Pharmacodynamic Steady State of Once Daily Tiotropium (18μg) Inhalation Capsule in Patients With Chronic Pulmonary Disease (COPD)
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 65
- Locations
- 5
- Primary Endpoint
- Peak FEV1 response, defined as the peak FEV1 minus the steady-state baseline FEV
Study Overview
Brief Summary
To evaluate acute effect of single dose of ipratropium (Atrovent) or fenoterol (Berotec) in comparison to placebo when given to COPD patients on pharmacodynamic steady state of tiotropium (Spiriva)
Detailed Description
In case mono-bronchodilator therapy does not control symptoms of COPD adequately or if regular maintenance therapy is desired, a therapeutic intervention with a combination of bronchodilators is recommended. The risks of side-effects increases with increasing dose of any drug and, therefore, the most important rationale for combination therapy is a very favourable ratio of efficacy and safety. Knowing that anticholinergic and beta-adrenergic agents achieve their bronchodilating effects by different mechanisms, in particular the combination of these agents has proven to be beneficial in the management of COPD. Based on the established clinical benefits, tiotropium is an attractive and promising agent for the first-line long-term maintenance therapy in COPD. This also implies that a therapeutic intervention with other bronchodilators will be prescribed in daily practice. At present no studies on combination therapy with short-acting agents are available. Therefore, using a double-blind, randomised, crossover design, the bronchodilator effects of single doses of ipratropium or fenoterol were compared with placebo when added on top of steady state tiotropium. Patients were pre-treated with tiotropium to achieve this pharmacodynamic steady state. Serial lung function tests (FEV1, FVC, Raw, sGaw) were conducted following add-on of the short-acting bronchodilators or placebo.
Study Hypothesis:
H0: there is no difference between treatments in mean peak FEV1 H1: there is a difference between treatments in mean peak FEV1
Comparison(s):
Add-on of placebo was compared to add-on of ipratropium or add-on of fenoterol. The comparison of ipratropium with placebo was primary. The other 2 pair-wise comparisons were secondary.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Double
Eligibility Criteria
- Ages
- 40 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •diagnosis of COPD
- •FEV1 < 60% of predicted
- •FEV1 < 70% of FVC
- •smoking history of 10 pack-years
Exclusion Criteria
- •significant other disease than COPD
- •history of asthma, allergic rhinitis or blood eosinophil count > 600mm3
- •cardiac arrhythmia requiring drug therapy
- •symptomatic prostatic hypertrophy, bladder neck obstruction or narrow-angle glaucoma
- •recent history of MI (within past year)
- •history of cancer within past 5 years
- •life-threatening pulmonary obstruction
- •cystic fibrosis or bronchiectasis; tuberculosis
- •pulmonary resection
Outcomes
Primary Outcomes
Peak FEV1 response, defined as the peak FEV1 minus the steady-state baseline FEV
Time Frame: up to 37 days
Secondary Outcomes
- Peak FVC response in the six-hour observation period following administration of the first single dose of randomised treatment(up to 37 days)
- FEV1 and FVC response one hour after the second dose of randomised treatment(up to 37 days)
- Individual FEV1 and FVC measurements at each time point(up to 37 days)
- sGaw and Raw measured at 1 and 6 hour after the first dose of randomised treatment and at 1 hour after the second dose of randomised treatment(up to 37 days)
- All adverse events(up to 37 days)
- Pulse rate(up to 37 days)
- Sitting blood pressure in conjunction with spirometry(up to 37 days)
- ECG recorded one hour after the first dose of randomised treatment(up to 37 days)
- Physical examination at baseline (Visit 1) and at the conclusion of patient participation in the trial(up to 37 days)